Countries reporting B.1.1.7 - Credit CDC
#15,874
While there are literally thousands of COVID variants around the world, only a small handful have been linked to increased transmissibility, increased severity, or antibody resistance. Of those, three stand out - B.1.1.7, B1.351, and P.1 - with the UK's B.1.1.7 variant being the most widespread and most studied of the group.
Although its increased transmissibility was apparent back in December, it wasn't until mid-January that we began to see reports of increased severity, hospitalization and/or death associated with this variant (see UK: NERVTAG paper on COVID-19 variant of concern B.1.1.7).
Initially this increased risk of death was pegged at 30%-40%, but since then we've seen a number of studies (see below) with higher estimates.
BMJ: Risk of Mortality in Patients Infected with SARS-CoV-2 VOC 202012/1 (B.1.1.7)
SSI: COVID Variant B.1.1.7 Increases Risk of Hospitalization 64%
Nature: LSHTM Study On Increased Mortality With COVID Variant B.1.1.7
While not everyone has fully embraced these estimates, citing confounders such as winter weather exacerbating comorbidities, it must be said we've seen remarkable consistency among their findings.
The full, open-access report is well worth reading and is too lengthy to post here. I've only selected some excerpts. So follow the link to read it in its entirety. I'll have a postscript when you return.
Rapid communication Open Access
Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February
Daniel J Grint1 , Kevin Wing1 , Elizabeth Williamson1 , Helen I McDonald1 , Krishnan Bhaskaran1 , David Evans2 , Stephen JW Evans1 , Alex J Walker2 , George Hickman2 , Emily Nightingale3 , Anna Schultze1 , Christopher T Rentsch1 , Chris Bates4 , Jonathan Cockburn4 , Helen J Curtis2 , Caroline E Morton2 , Sebastian Bacon2 , Simon Davy2 , Angel YS Wong1 , Amir Mehrkar2 , Laurie Tomlinson1 , Ian J Douglas1 , Rohini Mathur1 , Paula Blomquist5 , Brian MacKenna2 , Peter Ingelsby2 , Richard Croker2 , John Parry4 , Frank Hester4 , Sam Harper4 , Nicholas J DeVito2 , Will Hulme2 , John Tazare1 , Ben Goldacre2,6 , Liam Smeeth1,6 , Rosalind M Eggo1,6
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern B.1.1.7 (VOC) was first identified in Kent, United Kingdom (UK) in autumn 2020. Early analysis suggests it is more transmissible than previously circulating forms (non-VOC) [1]. It is now the dominant strain throughout the UK and is increasing in prevalence across Europe [2]. Early reports of increased mortality have not included data on individuals’ comorbidities, and this information is needed to facilitate pandemic planning.
Certain PCR assays for SARS-CoV-2 do not amplify one of the spike protein gene targets in this VOC. Spike gene target failure (SGTF) is therefore a proxy for VOC identification, with greater than 95% sensitivity for VOC diagnosis during the period from 16 November to 11 January [3].
Working on behalf of NHS England, we estimate the risk of death following confirmation of SARS-CoV-2 infection in England, comparing infection with VOC to non-VOC, after accounting for demographic factors and comorbidities. The code and configuration of our analysis is available online (github.com/opensafely/sgtf-cfr-research).
(SNIP)
Relative hazard of death
We calculated the relative hazard of death for VOC compared with non-VOC cases using a Cox proportional hazards regression model stratified by region (upper tier local authority area (UTLA)) [4,5]. Follow-up began at the date of testing positive for SARS-CoV-2 and was censored on 5 February 2021 or 7 days before receipt of a SARS-CoV-2 vaccine, whichever came first. The 7 days prior to vaccination were censored in this analysis to remove a potential immortal time bias because illness which may lead to death would exclude the booking of and administration of a vaccine. Infection with the VOC was consistently associated with an increased hazard of death.
In a fully adjusted analysis accounting for demographics and comorbidities, hazards were two-thirds higher in the VOC group (hazard ratio (HR): 1.67; 95% confidence interval (CI): 1.34–2.09; p < 0.0001) compared with non-VOC (Figure 1). Increased hazards for VOC were consistent across all pre-specified subgroup analyses including epidemiological week, age group, categorical number of comorbidities, ethnicity and index of multiple deprivation (IMD) quintile [6]. Increased hazards were also consistent across all pre-specified sensitivity analyses; in an analysis restricted to people testing positive for SARS-CoV-2 infection a minimum of 28 days before the censoring date, the hazard ratio was 1.71 (95% CI: 1.36–2.15; p < 0.0001).
Absolute risk of death by 28 days
We found a consistently higher absolute risk of death by 28 days after a SARS-CoV-2-positive test in all groups stratified by age, sex and presence of comorbidities in VOC, compared with non-VOC (Table 2). Risk of death was estimated by the marginal means of a fully adjusted logistic regression model. This analysis was restricted to 112,979 people diagnosed with SARS-CoV-2 a minimum of 28 days before the censoring date, with the outcome death by 28 days after a positive test. Deaths occurring beyond 28 days were censored. Data were not censored 7 days prior to vaccination in this analysis as vaccination is contraindicated in the month following a positive SARS-CoV-2 test. Consistent with the Cox model above, VOC was associated with increased odds of death in this model (adjusted odds ratio (AOR): 1.73; 95% CI: 1.34–2.23; p value < 0.0001, vs non-VOC).
The risk of death was low for people younger than 65 years in the absence of comorbidities; in this age group it was higher for male than female cases (VOC: males: 0.14%; females: 0.07% vs non-VOC: males: 0.09%; females: 0.05%). The risk of death was consistently higher for male cases and increased with age and the presence of comorbidities. The highest risk of death within 28 days was seen among those 85 years and older with two or more comorbidities: VOC: males 24.3%; females: 14.7%; non-VOC: males: 16.7%; females: 9.7%). The excess risk of death within 28 days for VOC compared with non-VOC is shown in Figure 2.
(SNIP)
Discussion
The SARS-CoV-2 B.1.1.7 VOC has been the subject of intense research since its emergence. Increased transmissibility means it is now the most common variant in the UK, a trend confirmed here. We found that this VOC was associated with two-thirds higher case fatality than the previously circulating virus in this unvaccinated population. For every three deaths in a population with the previously circulating virus we would expect five deaths in a similar population with VOC.Currently, roughly 97% of the COVID Variants of Concern (VOC) being tracked in the United States by the CDC are B.1.1.7, and the MMWR has forecast this variant to become the dominant COVID virus in the United States later this spring (see MMWR: Emergence Of SARS-CoV-2 B.1.1.7 Lineage — United States, Dec 29, 2020–Jan 12, 2021).Other studies have assessed the relative mortality of the VOC with similar conclusions [7-10], however, our results are the first to include detailed information on the presence of comorbidities. Interestingly, the effects of age and comorbidities appear to be collinear as adjustment for comorbidities did not alter the findings after adjustment for age. As prevalence of many comorbidities is associated with age, this finding appears plausible [11]. The consistency of the effect for each epidemiological week of diagnosis shows that the increase in mortality due to VOC could not be explained by other secular changes in mortality such as hospitals exceeding capacity.
While we are seeing some hopeful trends in the United States right now, Europe - where B.1.1.7 is already well established - is backsliding (see week 10 Epi Curve below), with some countries recently forced to reimpose lockdowns.
The progress we've made - bolstered by the successful rollout of over 100 million doses of the vaccine - is reassuring, but it is by no means guaranteed to continue. And with potentially a 67% higher fatality rate, even a relatively modest surge of new cases could do a lot of damage.
